Cachexia, featuring rapid loss of weight and muscle, is common to many complex diseases such as chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF) and cancer. Regardless of the primary disease diagnosis, the presence of cachexia is associated with poor prognosis. Equally important is the observation that not every patient diagnosed with a complex disease such as COPD and CHF becomes cachectic. This information motivated me to hypothesize that there are common genes and pathways influencing cachexia in these different complex, chronic traits. COPD is the third leading cause of death in the United States and it has been estimated that as high as 20% of COPD cases develop cachexia, however this number may be overestimated due to limitations associated with defining cachexia. The development of cachexia is a strong predictor of mortality. This study has three specific aims: 1) Identify genetic and genomic variants associated with cachexia and related traits in COPD; 2) Test for significant relationships between pectoralis muscle area (PMA), fat-free mass (FFM) and gene expression data in COPD cases; 3) Identify gene expression signatures associated with cachexia and PMA in COPD cases. As part of my K99 analyses, I took advantage of the availability of several well-characterized COPD populations in order to investigate markers of muscle wasting and cachexia such as low PMA and change in BMI. However, the field is in need of investigations focused on cohorts of COPD cases phenotyped for muscle wasting and cachexia. The development of such a cohort is a key focus of the R00 phase of her application (Aim 2) and will lead to pilot data for her first R01 applications.